Immunosuppression with FK506 has no influence on fracture healing in the rat
Immunosuppression with FK506 has no influence on fracture healing in the rat
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DOI：
10.1016/j.bone.2005.04.024
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发表时间：
2005-08-01
期刊：
影响因子：
4.1
通讯作者：
Obertacke, U
中科院分区：
文献类型：
--
作者：
Voggenreiter, G;Siozos, P;Obertacke, U
免疫抑制剂如环孢素A和FK 506广泛用于实体器官移植。它们加速骨重建，但导致净骨丢失。本研究的目的是研究FK 506对大鼠骨折愈合的影响。将80只刘易斯大鼠分为4组，在制造闭合、非移位性单侧胫骨骨折后开始接受FK 506（1 mg/kg BW）或不给药2周或4周。影像学、组织学和生物力学研究用于评价骨折愈合，并对完整对侧胫骨干骺端进行组织形态计量学分析。第2周和第4周时，X线片显示对照组骨折愈合与FK 506治疗组骨折愈合无差异。测试的对侧完整胫骨和骨折骨痂的力学参数表明对照组和免疫抑制组动物之间无差异。胫骨骨组织形态计量学显示骨形成和骨吸收增加，同时骨小梁面积百分比显著减少。在4周时，骨折显示骨愈合，骨折部位有编织骨，只有少量软骨。在两个时间点，对照组和FK 506组的组织学分级无差异。我们的结论是，全身应用FK 506对大鼠实验性骨折愈合没有生物力学和组织学影响。然而，吸收远远超过形成导致胫骨骨小梁中的净骨丢失，这对完整骨的稳定性没有影响。(c)2005年爱思唯尔公司All rights reserved.
Immunosuppressant drugs like cyclosporine A and FK506 are widely used for solid organ transplantation. They are accelerating bone remodeling but cause net bone loss. The aim of this study was to investigate the effect of FK506 on fracture healing in the rat. Eighty Lewis rats were divided into four groups, which received FK506 (1 mg/kg BW) or no treatment for 2 or 4 weeks, beginning after production of a closed, nondisplaced unilateral tibial fracture. Radiographic, histological, and biomechanical studies were used to evaluate fracture healing and histomorphometric analysis of the tibial metaphysis of the intact contralateral side was performed. Radiographs revealed no difference of the healing of the control fractures compared with the fractures in the FK506-treated group at 2 and 4 weeks. The mechanical parameters of the tested contralateral intact tibiae and of the fracture callus demonstrated no difference between control and immunosuppressed animals. Tibial bone histomorphometry revealed increased measures of bone formation and bone resorption, accompanied by a significant reduction of percent trabecular area. At 4 weeks, the fractures showed osseous healing with woven bone at the fracture site and only minimal amounts of cartilage. Histological grading was not different between the control and the FK506 group at both time points. We conclude that systemic application of FK506 has no biomechanical and histological effects of experimental fracture healing in the rat. However, resorption far in excess of formation leads to a net bone loss in the trabecular bone of the tibia that has no effect on the stability of the intact bone. (c) 2005 Elsevier Inc. All rights reserved.